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R Quirion

Publications and source records attributed to R Quirion.

At least 325 records · Page 18Linked to original sources
PubMed1987

Autoradiographic distribution of non-dopaminergic binding sites labeled by [3H]haloperidol in rat brain.

The regional distribution of binding sites labeled by [3H]haloperidol, in the presence of excess spiroperidol, was compared to the regional distribution of receptors labeled by [3H]SCH 23390 and [3H]sulpiride, [3H]SCH 23390 and [3H]sulpiride labeled distinct nuclei, such as the olfactory tubercle, caudate, globus pallidus, substantia nigra, and inferior and superior colliculi. In contrast, the distribution of binding sites labeled by [3H]haloperidol, in the presence of excess spiroperidol, were much more extensive. Some areas containing the highest density of sites labeled by [3H]haloperidol were the external plexiform layer of the olfactory bulb, the cerebral cortex, the paraventricular nuclei, the interpeduncular nucleus and the superior colliculus. The distribution of non-dopaminergic binding sites labeled by haloperidol was clearly quite different from that labeled by dopaminergic ligands.

Animals↗
PubMed1987

Differential effects of selective lesions of cholinergic and dopaminergic neurons on serotonin-type 1 receptors in rat brain.

Serotonin (5-HT)-type1 (abbreviated as a subscript 1) receptor binding sites are discretely distributed in rat brain. High densities of [3H]5-HT1 binding sites are especially located in areas enriched with cholinergic and dopaminergic innervation, such as the substantia innominata/ventral pallidum, striatum, septal nuclei, hippocampus and substantia nigra. The possible association of [3H]5-HT1 binding sites with cholinergic or dopaminergic cell bodies and/or nerve fiber terminals was investigated by selective lesions of the substantia innominata/ventral pallidum-cortical and septohippocampal cholinergic pathways and the nigrostriatal dopaminergic projection. [3H]5-HT1 receptor binding sites are possibly located on cholinergic cell bodies in the ventral pallidum-cortical pathway since [3H]5-HT1 binding in the substantia innominata/ventral pallidal area was markedly decreased following kainic acid lesions. Fimbriaectomies markedly decreased [3H]5-HT1 binding in the hippocampus, suggesting the presence of 5-HT1 binding sites on cholinergic nerve fiber terminals in the septohippocampal pathway. Lesions of the nigrostriatal dopaminergic projection did not modify [3H]5-HT1 binding in the substantia nigra and the striatum, suggesting that 5-HT1 receptors are not closely associated with dopaminergic cell bodies and nerve terminals in this pathway. These results demonstrate differential association between 5-HT1 receptors and cholinergic and dopaminergic innervation in rat brain.

Acetylcholine↗
PubMed1987

Characterization and autoradiographic distribution of hemicholinium-3 high-affinity choline uptake sites in mammalian brain.

[3H]hemicholinium-3 (HC-3) binding characteristics have been investigated using membrane binding assays and in vitro receptor autoradiography. In rat brain membrane preparations, [3H]HC-3 binds with high affinity to an apparent single class of sites. [3H]HC-3 binding is Na+-dependent. The ligand selectivity pattern strongly suggests that [3H]HC-3 selectivity labels the high affinity choline uptake (HACU) in brain membranes (HC-3 greater than choline greater than carbamylcholine greater than acetylcholine). This hypothesis is also supported by quantitative autoradiographic data which demonstrate that the discrete distribution of [3H]HC-3 binding sites correlates very well with the known distribution of other cholinergic markers such as choline acetyltransferase (ChAT), acetylcholinesterase (AChE), HACU, and [3H]AH-5183 (blocker of the vesicular transport of acetylcholine). For example, high densities of labelling are observed for these different markers in the interpeduncular nucleus, anteroventral nucleus of the thalamus, striatum, basolateral nucleus of the amygdala, and an exquisite laminar distribution in the hippocampus. Similar autoradiographic distributions of [3H]HC-3 binding sites are observed in other mammalian species such as guinea pig and monkey. Finally, 7-day unilateral kainic acid lesions of the nucleus basalis magnocellularis (nbm) decrease cortical [3H]HC-3 binding and ChAT activity, although not to a similar extent. In summary, these results demonstrate that [3H]HC-3 is a selective ligand of the HACU in mammalian brain. Thus, it is now possible to characterize precisely various structural components of the cholinergic synapses using markers such as [3H]HC-3, ChAT, HACU, [3H]AH-5183, and selective muscarinic and nicotinic receptor radioligands.

Animals↗
PubMed1987

Human brain receptor autoradiography using whole hemisphere sections: a general method that minimizes tissue artefacts.

A general method for the preparation of high-quality, mostly ice-crystal-artefact-free whole human brain hemisphere sections is described. Upon receipt, hemispheres are divided; one is then fixed in buffered 10% formalin for neuropathological analysis while the other is cut in 8-10-mm-thick coronal slices that are then rapidly frozen in 2-methylbutane at -40 degrees C (10-15 sec) before being placed in the brain bank at -80 degrees C. Such rapid freezing markedly decreases the formation of ice-crystal artefacts. Whole-hemisphere 20-micron thick sections are then cut and mounted onto lantern-type gelatin-coated slides. These sections are subsequently used for both qualitative and quantitative in vitro receptor autoradiography. Examples of data obtained are given by using various radioligands labelling "classical" neutrotransmitter, neuropeptide, enzyme, and ion channel receptor binding sites. This method should be useful for the obtention of various receptor maps in human brain. Such information could be most useful for in vivo receptor visualization studies using positron emission tomography (PET) scanning. It could also indicate if a given receptor population is specifically and selectively altered in certain brain diseases, eventually leading to the development of new therapeutic approaches.

Adult↗
PubMed1987

Neurotensin receptor binding sites in monkey and human brain: autoradiographic distribution and effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.

Neurotensin (NT) receptor binding sites were characterized and localized by using membrane binding assay and in vitro receptor autoradiography in monkey and human brain. Additionally, the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment on NT binding sites were investigated in monkey. [125I]Tyr3-NT ([125I]NT) apparently binds to a single class of high-affinity sites (Kd in nanomolar range) in both species. Ligand selectivity patterns strongly suggest that the structural requirements of both monkey and human brain NT receptors are very similar to those previously reported in other tissues, such as those of the rat brain and rat stomach. In monkey brain, [125I]NT binding sites are discretely distributed with high densities of sites found in the cingulate cortex, amygdala, hippocampus, ventral tegmental area, substantia nigra, and periaqueductal gray matter. A similar pattern is observed in the human brain. However, the laminar distribution of [125]NT binding sites in cortex varies between monkey and human brain. In monkey brain, [125I]NT binding sites are mostly concentrated in deep cortical layers while the laminar distribution of NT sites changes with cortical areas in human brain. The densities of [125I]NT binding sites are markedly decreased in the caudate, putamen, and substantia nigra in MPTP-treated monkeys. These results suggest strong interactions between NT and dopaminergic systems in both monkey and human brain tissues.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Localization of kappa opioid receptor binding sites in human forebrain using [3H]U69,593: comparison with [3H]bremazocine.

1. The autoradiographic distribution of kappa opioid receptor binding sites in human brain was examined using two radiolabeled probes, namely [3H]U69,593 and [3H]bremazocine. 2. [3H]U69,593 binding was performed in the absence of blockers for other sites, while [3H]bremazocine binding was investigated in the presence of saturating concentrations of mu and delta blockers to ensure selective labeling of kappa opioid receptors. 3. Our results show that the autoradiographic distribution of [3H]U69,593 and [3H]bremazocine (plus blockers) binding sites is identical, with high densities of sites found in deep cortical layers and claustrum. 4. This indicates that [3H]U69,593 is a highly selective ligand of the kappa opioid receptor type.

Autoradiography↗
PubMed1987

Platelet imipramine binding in patients with panic disorder and major familial depression.

Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression. Thus, despite previous findings of an overlap between panic and depressive disorders, the present results suggest that the two syndromes may have distinct neurochemical substrates.

Adult↗
PubMed1987

Structure-activity studies of C- and N-terminal fragments of cholecystokinin 26-33 in guinea pig isolated tissues.

In vitro structure-activity studies with cholecystokinin (CCK)/gastrin-related peptides, including C- and N-terminal fragments of CCK 26-33, were undertaken in guinea pig gallbladder and ileum. The general order of potency in both smooth muscle preparations is CCK 26-33 greater than CCK 1-33 greater than 27-33 much much greater than nonsulfated (NS) CCK 26-33 greater than pentagastrin greater than CCK 30-33. None of the CCK fragments exhibit antagonistic properties such as in guinea pig, rat and mouse pancreatic acinar cells and hog duodenum. These observations suggest the existence of CCK receptor sub-types in peripheral tissues.

Animals↗
PubMed1987

Effect of apomorphine on melatonin secretion in normal subjects.

There is some evidence in animals that dopamine (DA) affects melatonin secretion. The effect of apomorphine (Apo), a selective DA receptor agonist, and placebo on day-time melatonin secretion was studied in six normal men. Apo HCl in a dose (0.5 mg sc) which increased growth hormone secretion in all subjects had no effect on day-time melatonin concentrations in plasma. In keeping with other clinical studies these data suggest that melatonin secretion is not regulated by a DA mechanism in man.

Adolescent↗
PubMed1987

Muscarinic, benzodiazepine, GABA, chloride channel and other binding sites in frontal cortex in hepatic coma in man.

Alterations in several neurotransmitter systems in brain have been implicated in the pathophysiology of hepatic coma (HC). Studies on human autopsy material are few. We investigated 3H-quinuclidinylbenzilate (QNB), 3H-spiperone, 3H-imipramine, 3H-PN-200-110, 3naloxone, 3H-flunitrazepam, 3H-muscimol, 35S-t-butylbicyclophosphothionate and 3H-cyclohexyladenosine binding sites in frontal cortex from seven patients with HC and five controls. The density of 3H-QNB binding sites was significantly decreased and the affinity slightly increased in HC. The functional significance of these selective changes in muscarinic receptor binding sites is unclear. Further studies evaluating cholinergic function in HC are indicated. Acute studies in animals point to an increase in GABA and BZ binding sites in HC. The present results show that the BZ/GABA-receptor-chloride-ionophore complex is unchanged in HC in man. Serotonergic (5HT-2), adenosine (A-1), imipramine (5HT uptake sites), opiate (naloxone) and calcium channel antagonist binding sites are unchanged in HC.

Adenosine↗
PubMed1987

Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain.

Receptor binding parameters and autoradiographic distribution of various opioid receptor sites have been investigated in normal human brain, post-mortem. [3H]DAGO, a highly selective mu ligand, binds to a single class of high affinity (Kd = 1.1 nM), low capacity (Bmax = 160 fmol/mg protein) sites in membrane preparations of frontal cortex. These sites show a ligand selectivity profile that resembles that of the mu opioid receptor. On the other hand, [3H]bremazocine, in presence of saturating concentrations of mu and delta blockers, appears to selectively bind to a single population of kappa opioid sites (Kd = 0.13 nM; Bmax = 93.0 fmol/mg protein) in human frontal cortex. Whole hemisphere in vitro receptor autoradiography reveals that [3H]DAGO-mu, [3H]DSLET-delta and [3H]bremazocine (plus blockers)-kappa binding sites are discretely and differentially distributed in human forebrain. In the cortex, mu sites are concentrated in laminae I and IV, delta sites in laminae I and II while kappa sites are found in deeper layers (laminae V and VI). In subcortical nuclei, high densities of mu and delta sites are seen in the caudate and putamen while high amounts of kappa sites are present in the claustrum and amygdala. The nucleus basalis of Meynert is enriched in all three classes of sites while the globus pallidus only contains moderate densities of kappa sites. Thus, the possible alterations of these various classes of opioid receptors in neurological and psychiatric diseases certainly deserve further investigation.

Aged↗
PubMed1987

Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake.

A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific [3H]hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.

Animals↗
PubMed1986

Neurotensin binding sites in the forebrain and midbrain of the pigeon.

An autoradiographic method was used to assess the distribution of binding sites for [3H]neurotensin (NT) in the forebrain and midbrain of the pigeon. Within the telencephalon the highest levels of NT binding sites were observed within the hyperstriatum ventrale (HV). Moderate to high levels of NT binding were observed within the archistriatum, neostriatum intermedium, and hyperstriatum accessorium. These telencephalic regions and HV are thought to be comparable to portions of mammalian neocortex. Lower levels of binding sites were observed within the striatal complex including the laterally situated paleostriatum augmentatum and medially situated lobus parolfactorius. The lowest levels of NT binding sites in the telencephalon were observed within the paleostriatum primitivum (PP, considered comparable to mammalian globus pallidus), ectostriatum (comparable to layer IV of mammalian extrastriate visual cortex), field "L" (comparable to layer IV of mammalian auditory cortex), hippocampus, septum, and preoptic area. Despite considerable regional variation, the overall level of NT binding throughout the pigeon telencephalon appears to be significantly higher than that reported for mammals, particularly within pallial areas. Within the brainstem, moderate levels of NT binding sites were observed in the lateral habenular nuclei, the ventral tegmental area of Tsai, nucleus tegmentipedunculopontinus, pars compacta (comparable to the mammalian substantia nigra, pars compacta), locus coeruleus, and the nucleus subcoeruleus dorsalis. The latter four cell groups contain numerous catecholaminergic neurons. Corresponding catecholaminergic cell groups in mammalian forms also contain high levels of NT receptors. As in mammals, lower levels of NT binding were observed in most diencephalic nuclei. Somewhat higher levels of NT binding were observed within the pretectal nuclei spiriformis lateralis and spiriformis medialis. Moderate levels of NT binding sites were observed within the retinal terminal layers of the tectum (i.e., layers 1-7). Immunohistochemical experiments (Reiner and Carraway; Brain Res. 341:365-371, '85; Reiner: ARVO Abstracts: p. 185, '86) localizing NT and a related hexapeptide, LANT6, have shown that LANT6 is present in retinal ganglion cells, in cells of the paleostriatum, and in the striatotegmental and striatopretectal fiber pathways of the pigeon. Thus some features of the NT binding observed here in pigeon brain including the existence of substantial NT binding sites in the brainstem catecholamine nuclei, pretectum (nucleus spiriformis lateralis), and optic tectum may reflect the existence, at least in part, of functional receptors for LANT6.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Autoradiographic distribution of phencyclidine receptors in the rat brain using [3H]1-(1-(2-thienyl)cyclohexyl)piperidine ([3H]TCP).

The distribution of phencyclidine (PCP) receptors in the rat brain was determined by autoradiography using 1-(1-(2-thienyl)cyclohexyl)piperidine ([3H]TCP). [3H]TCP appeared to bind to PCP receptors as only PCP-like drugs and sigma-opioids inhibited the binding of [3H]TCP. The areas of the rat brain with the highest density of radiolabeled binding sites were the superficial layers of cerebral cortex, hippocampus and dentate gyrus. Moderate densities of binding sites were found in the medial geniculate nuclei, caudate nucleus, nucleus accumbens, interpeduncular nucleus, superior colliculus, periaqueductal gray and cerebellum. Low densities of binding sites were observed in spinal cord, most of the brainstem, the substantia nigra and most of the hypothalamus.

Animals↗
PubMed1986

Antemortem laboratory diagnosis of Alzheimer's disease.

The accuracy of diagnosis for AD by conventional clinical and laboratory means is in the order of 80%. Neurophysiological techniques (EEG, evoked potentials) show abnormalities in AD that could prove to be useful for diagnosis after pharmacological challenges. CSF analysis show a reduction of the concentration of various neuropeptides, reduction shared by other types of dementias. Among the existing imaging techniques PET using 18F-fluorodeoxyglucose is the most diagnostic in AD because of the early and often asymmetrical decrease in parietotemporal metabolic activity. Cortical biopsy with histological and biochemical analysis can provide an accurate in vivo diagnosis of AD.

Alzheimer Disease↗
PubMed1986

Nucleus basalis neuronal loss, neuritic plaques and choline acetyltransferase activity in advanced Alzheimer's disease.

All our advanced, severe cases of Alzheimer's disease have dramatic cholinergic cell losses in the nucleus basalis of Meynert even after correction for cell or nucleoli shrinkage. There is a good correlation between choline acetyltransferase activity and "healthy" cell number in the nucleus basalis of Meynert. Half of the Alzheimer disease cases have markedly reduced cortical choline acetyltransferase activity in spite of preserved nucleus basalis of Meynert choline acetyltransferase activity, suggesting a deficiency of cortical origin and/or of axonal transport in Alzheimer disease. The relationship between cell loss in the various sub-divisions of the nucleus basalis of Meynert and plaque counts in corresponding and non-corresponding projection areas of the cortex has also been examined. Globally, this relation appears more obvious when cell loss in a sub-division of the nucleus basalis of Meynert is compared to plaque counts in its cortical projection area. However, the relation is discontinuous with few or no data to document the intermediary stages of the process, probably reflecting the severity of our Alzheimer disease cases.

Aged↗